bloodstream infections due to ESBL- producing Escherichia coli
Conditions
Interventions
Study drug: cefmetazole sodium Cefmetazole 1g intravenously (over 30 minutes) every 8 hours. For 5 day to 14 days.
Control drug: Meropenem hydrate Meropenem 1g intravenously (over 30 minutes) every
Sponsors
Japan Institute for Health Security
Fujita Health University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Patient or whose legal representatives provided written informed consent for the study participation 2) Persons who are 18 years of age or older at the time of obtaining consent 3) Within 72 hours from the time of the first blood culture collection 4) E. coli isolated from blood meetsany of the following 1. ceftriaxone or cefotaxime-resistant (MIC 2mg/L or higher), meropenem-sensitive (MIC 1mg/L or lower), and cefmetazole MIC 16mg/L or lower 2. E. coli and CTX-M gene are positive in the genetic testing system and any carbapenemase gene is negative 3. ESBL productivity of E. coli is confirmed or strongly suspected (e.g. ESBL pattern in beta-lactamase detection kit or ESBL screening medium test positive) If a patient is enrolled by meeting criteria 4) 2 or 4) 3, however, later, 4) 1 is found out not to be satisfied, then, the participation in the study will be discontinued.
Exclusion criteria
Exclusion criteria: 1) Participation in other intervention studies 2) History of allergy to cefmetazole or carbapenem 3) Bacteremia due to multiple bacteria (excluding skin contaminants) 4) Patients expected to die within 4 days after randomization (randomized day = day 1) 5) Patients who are expected to be difficult to follow during the first 30 days after randomization (day of randomization = day 1) 6) Pregnant women and breastfeeding women 7) Patients on dialysis or patients whose creatinine clearance (based on Cockcroft-Gault formula) is less than 10ml/min 8) Patients expected to receive additional antibiotics active against Gram-negative bacilli by day 5 after randomization (excluding sulfamethoxazole and trimethoprim for prevention of Pneumocystis pneumonia) (day of randomization = Day 1) 9) Confirmed or strongly suspected carbapenemase-producing or AmpC-producing E. coli from blood culture (e.g. carbapenemase-positive with carbapenemase detection kit or AmpC pattern-positive with beta-lactamase detection kit, carbapenemase screening medium positive) 10) Patients currently using sodium valproate or expected to use it by day 5 after randomization (randomized day = day 1) 11) Persons who are judged inappropriate for inclusion in the research by the principal investigator at each test site
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 30-day all-cause mortality of cefmetazole and meropenem after bloodstream infection (randomized day = day 1) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1) 14-day all-cause mortality of cefmetazole and meropenemafter bloodstream infection (randomized day = day 1) 2) Microbiological success rate: defined as negative blood cultures taken on or before day 5 (randomized day = day 1). 3) Clinical success rate: resolution of fever (body temperature [axillary temperature] 37.5 Celsius or higher) and leukocytosis (WBC>12000/micro-liter) on or before day 5 (randomized days = day 1) 4) clinical and microbiological success rate: 2) and 3) 5) Time to resolution of fever: Number of days from randomization to resolution of fever (eg, if fever resolved on the next day of randomization, count as 1 day). Resolution of fever is defined as temperature less than or equal to 37.5 Celsius for at least 24 hours.The first day when the temperature becomes below 37.5 Celsius is recorded. 6) Recurrence of bloodstream infection: Bloodstream infection due to ESBL-producing E. coli by day 30 after the end of the study drug administration period (randomized day = day 1) 7) Detection rate of carbapenem-resistant bacteria or cefmetazol-resistant bacteria, or incidence of Clostridioides difficile infection: Isolation of carbapenem-resistant organisms (CROs) or cefmetazole resistant organisms (CMZROs) from clinical specimens (excluding specimens for surveillance purposes) or positive stool tests for C. difficile toxin from day 5 of study drug administration to day 30 of randomization. 8) Ordinal scale evaluation by Desirability of Outcome Ranking (DOOR) | — |
Countries
Japan
Contacts
Public ContactKayoko Hayakawa
Japan Institute for Health Security Disease Control and Prevention Center
Outcome results
None listed