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

Abstract

Background: Rapid blood culture diagnostics are of unclear benefit for patients with gram-negative bacilli (GNB) bloodstream infections (BSIs). We conducted a multicenter, randomized, controlled trial comparing outcomes of patients with GNB BSIs who had blood culture testing with standard-of-care (SOC) culture and antimicrobial susceptibility testing (AST) vs 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 (AS) review or RAPID with AS. The primary outcome was time to first antibiotic modification within 72 hours of randomization.

Results: Of 500 randomized patients, 448 were included (226 SOC, 222 RAPID). Mean (standard deviation) time to results was faster for RAPID than SOC for organism ID (2.7 [1.2] vs 11.7 [10.5] hours; P < .001) and AST (13.5 [56] vs 44.9 [12.1] hours; P < .001). Median (interquartile range [IQR]) time to first antibiotic modification was faster in the RAPID arm vs the SOC arm for overall antibiotics (8.6 [2.6-27.6] vs 14.9 [3.3-41.1] hours; P = .02) and gram-negative antibiotics (17.3 [4.9-72] vs 42.1 [10.1-72] hours; P < .001). Median (IQR) time to antibiotic escalation was faster in the RAPID arm vs the SOC arm for antimicrobial-resistant BSIs (18.4 [5.8-72] vs 61.7 [30.4-72] hours; P = .01). There were no differences between the arms in patient outcomes.

Conclusions: Rapid organism ID and phenotypic AST led to faster changes in antibiotic therapy for gram-negative BSIs.

Clinical trials registration: NCT03218397.

Keywords: antibiotic susceptibility testing; blood cultures; bloodstream infection; gram negative; rapid diagnostic.

Figure 1.

Participant screening and randomization. The total population was used to evaluate rapid test performance and included patients who met eligibility criteria at the time of randomization regardless if they were later found to meet exclusion criteria. The mITT population included patients who met all eligibility criteria and no exclusion criteria. Abbreviations: GNB, gram-negative bacilli; mITT, modified intention-to-treat; RAPID, organism identification and phenotypic antibiotic susceptibility testing using the Accelerate Pheno System.

Figure 2.

Time from randomization to antibiotic changes by treatment arm in the modified intention-to-treat population. A, Time from randomization to first antibiotic modification by treatment arm. For patients who died within 72 hours, the time of earliest antibiotic modification was used as the time to modification. Patients who did not have antibiotic modifications were assigned a time of 72 hours. No censoring was observed. Includes time to first antibiotic modification for 8 patients who died within 72 hours of randomization. B, Time from randomization to first gram-negative antibiotic modification by treatment arm. Patients who did not have gram-negative antibiotic modifications were assigned a time of 72 hours. Includes time to first gram-negative antibiotic modification for 8 patients who died within 72 hours of randomization. C, Time from randomization to first antibiotic escalation in gram-negative or gram-positive antibiotics by treatment arm and isolate resistance. Resistance is defined as third-generation cephalosporin nonsusceptible Enterobacterales, carbapenem-resistant Enterobacterales, or carbapenem-resistant Pseudomonas species. Isolates with intermediate susceptibility were considered resistant. Resistant organisms: n = 36 for SOC and 40 for RAPID. Susceptible organisms: n = 190 for SOC and 182 for RAPID. Patients who did not have antibiotic escalation were assigned a time of 72 hours. Antibiotic escalation was assessed by local stewardship providers. D, Time from randomization to first antibiotic deescalation in gram-negative or gram-positive antibiotics by treatment arm and isolate resistance. Resistance is defined as third-generation cephalosporin nonsusceptible Enterobacterales, carbapenem-resistant Enterobacterales, or carbapenem-resistant Pseudomonas species. Isolates with intermediate susceptibility were considered resistant. Resistant organisms: n = 36 for SOC and 40 for RAPID. Susceptible organisms: n = 190 for SOC and 182 for RAPID. Patients who did not have antibiotic deescalation were assigned a time of 72 hours. Antibiotic deescalation was assessed by local stewardship providers. Abbreviations: AST, antibiotic susceptibility testing; CI, confidence interval; GN, gram-negative; IQR, interquartile range; Org, organism; RAPID, organism identification and phenotypic AST using the Accelerate Pheno System; s.d., standard deviation; SOC, standard-of-care culture.