Effect of dRAST on Treatment for Bacteremia in Patients With Hematologic Diseases

Effect of Direct Rapid Antibiotic Susceptibility Testing (dRAST) on Treatment for Bacteremia in Patients With Hematologic Diseases: Randomized Controlled Trial

The purpose of this study is to evaluate whether the use of direct rapid antibiotic susceptibility test (dRAST), in addition to the current standard antibiotic susceptibility test, can increase the proportion of patients with hematologic disease who received appropriate antibiotics in early period of bacteremia.

Study Overview

• Status: Completed
• Conditions: Hematologic Diseases; Bacteremia Sepsis
• Intervention / Treatment: Diagnostic test: dRAST; Diagnostic test: Current standard method

Detailed Description

• patients with hematologic diseases who have high risk of bacteremia, because of immune suppression treatment or intensive chemotherapy or bone marrow transplantation which these patients had received, will be recruited in tertiary referral medical centers.
• All the participants will be randomly assigned into either dRAST group or current standard antibiotic susceptibility test group.
• All the participants in the both arms will receive antimicrobial stewardship by infectious disease specialists. Antimicrobial stewardship will be performed at each timepoint of Gram stain results reporting, dRAST results reporting, and current method reporting.
• Target numbers are 58 and 58, respectively.
• All the participants will be monitored for general medical conditions such as vital sign and response to antibiotic treatment by infectious disease specialists for 1 week.
• The percentage of patients who received optimal targeted antibiotics 72 hours after blood collection for blood culture will be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who are expected to be admitted for more than 2 days due to treatment or complications of hematologic diseases (acute leukemia, chronic leukemia, myelodysplastic syndrome, lymphoma, multiple myeloma, aplastic anemia, etc.) in Seoul National University Hospital.
• Patients with confirmed bacteremia
• Patients who can understand the details of the clinical trial's explanation and provide the written consent

Exclusion Criteria:

• Patients who are expected to stay in the hospital within 2 days
• Patients without bacteremia during hospitalization
• Patients who show fungemia without evidence of bacteremia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: dRAST; Hematologic patients with bacteremia will receive antibiotics based on "dRAST" results.	Diagnostic test: dRAST; Infectious diseases specialists will do active antimicrobial stewardship according to dRAST results in addition to Gram staining results and current standard method.
ACTIVE_COMPARATOR: Current standard method; Hematologic patients with bacteremia will receive antibiotics based on current standard method results.	Diagnostic test: Current standard method; Infectious diseases specialists will do active antimicrobial stewardship according to Gram staining results, and current standard method without dRAST results.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients receiving optimal targeted antibiotics 72 hours after blood collection for blood culture	The percentage of patients receiving optimal targeted antibiotics antibiotics which is defined as most effective and narrowest antibiotics based on susceptibility testing results, 72 hours after blood collection for blood culture	72 hour after blood culture collection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to optimal targeted antibiotics	The time to the optimal targeted antibiotics administration after blood culture collection	Time from first blood culture collection up to 1 month
Amount of broad-spectrum antibiotics use	The duration of use of major antibiotics (vancomycin, carbapenem)	Time from first blood culture collection up to 1 week
Time to defervescence	Time from the time of blood culture collection to the time of fever resolution	Time from first blood culture collection up to 1 month
proportion of positive blood culture 48 hours after first blood culture	proportion of positive blood culture 48 hours after first blood culture	Time from blood culture collection up to 1 month
30-day mortality rate related with bacteremia	30-day mortality rate related with bacteremia	Time from blood culture collection up to 30-day
Percentage of patients receiving optimal targeted antibiotics 48 hours after	The percentage of patients receiving optimal targeted antibiotics antibiotics which is defined as most effective and narrowest antibiotics based on susceptibility testing results, 48 hours after blood collection for blood culture	48 hour after blood culture collection
Percentage of patients receiving unnecessary broad spectrum antibiotics 48 hours after	The percentage of patients receiving unnecessary broad spectrum antibiotics which is defined as administration of antibiotics to which organisms were susceptible, but had broad-spectrum activity requiring de-escalation or discontinuing administration, 48 hours after blood collection for blood culture	48 hour after blood culture collection
Percentage of patients receiving unnecessary broad spectrum antibiotics 72 hours after	The percentage of patients receiving unnecessary broad spectrum antibiotics which is defined as administration of antibiotics to which organisms were susceptible, but had broad-spectrum activity requiring de-escalation or discontinuing administration, 72 hours after blood collection for blood culture	72 hour after blood culture collection
Percentage of patients receiving ineffective antibiotics 48 hours after	The percentage of patients receiving ineffective antibiotics which is defined if the organisms were not susceptible, 48 hours after blood collection for blood culture	48 hour after blood culture collection
Percentage of patients receiving ineffective antibiotics 72 hours after	The percentage of patients receiving ineffective antibiotics which is defined if the organisms were not susceptible, 72 hours after blood collection for blood culture	72 hour after blood culture collection

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: wbpark1@snu.ac.kr Park, M.D., PhD., Seoul National University Hospital

Publications and helpful links

General Publications

• Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589-96. doi: 10.1097/01.CCM.0000217961.75225.E9.
• Choi J, Yoo J, Lee M, Kim EG, Lee JS, Lee S, Joo S, Song SH, Kim EC, Lee JC, Kim HC, Jung YG, Kwon S. A rapid antimicrobial susceptibility test based on single-cell morphological analysis. Sci Transl Med. 2014 Dec 17;6(267):267ra174. doi: 10.1126/scitranslmed.3009650.
• Choi J, Jeong HY, Lee GY, Han S, Han S, Jin B, Lim T, Kim S, Kim DY, Kim HC, Kim EC, Song SH, Kim TS, Kwon S. Direct, rapid antimicrobial susceptibility test from positive blood cultures based on microscopic imaging analysis. Sci Rep. 2017 Apr 25;7(1):1148. doi: 10.1038/s41598-017-01278-2.
• Huh HJ, Song DJ, Shim HJ, Kwon WK, Park MS, Ryu MR, Cho EH, Oh J, Yoo IY, Lee NY. Performance evaluation of the QMAC-dRAST for staphylococci and enterococci isolated from blood culture: a comparative study of performance with the VITEK-2 system. J Antimicrob Chemother. 2018 May 1;73(5):1267-1271. doi: 10.1093/jac/dky015.
• Garnacho-Montero J, Aldabo-Pallas T, Garnacho-Montero C, Cayuela A, Jimenez R, Barroso S, Ortiz-Leyba C. Timing of adequate antibiotic therapy is a greater determinant of outcome than are TNF and IL-10 polymorphisms in patients with sepsis. Crit Care. 2006;10(4):R111. doi: 10.1186/cc4995.
• Bauer KA, Perez KK, Forrest GN, Goff DA. Review of rapid diagnostic tests used by antimicrobial stewardship programs. Clin Infect Dis. 2014 Oct 15;59 Suppl 3:S134-45. doi: 10.1093/cid/ciu547.
• Renders NH, Kluytmans JA, Verbrugh HA. Clinical impact of rapid in vitro susceptibility testing and bacterial identification. J Clin Microbiol. 1995 Feb;33(2):508. doi: 10.1128/jcm.33.2.508-508.1995. No abstract available.
• Klastersky J, Ameye L, Maertens J, Georgala A, Muanza F, Aoun M, Ferrant A, Rapoport B, Rolston K, Paesmans M. Bacteraemia in febrile neutropenic cancer patients. Int J Antimicrob Agents. 2007 Nov;30 Suppl 1:S51-9. doi: 10.1016/j.ijantimicag.2007.06.012. Epub 2007 Aug 8.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2018
• Primary Completion (ACTUAL): September 15, 2019
• Study Completion (ACTUAL): October 10, 2019

Study Registration Dates

• First Submitted: July 26, 2018
• First Submitted That Met QC Criteria: August 1, 2018
• First Posted (ACTUAL): August 2, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 14, 2019
• Last Update Submitted That Met QC Criteria: October 11, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Bacteremia; Antimicrobial stewardship; Optimal targeted antibiotics; Antibiotic susceptibility test
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Bacteremia; Hematologic Diseases
• Other Study ID Numbers: 1806-173-955

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are not planning to share IPDs publically, but de-identified individual participant data for all outcome measures could be shared with other researchers under their request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No