Clinical trial NCT05102162: BL Infusion Trial:Beta-lactam Continuous Versus Intermittent Infusion and Associated Bacterial Resistance and Therapy Outcomes in Critically Ill Patients With Severe Pneumonia
Official title: Beta-lactam Continuous Versus Intermittent Infusion and Associated Bacterial Resistance and Therapy Outcomes in Critically Ill Patients With Severe Pneumonia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Pneumonia
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Food and Drug Administration (FDA)
First posted: 2021-11-01
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study plans to randomize a total of 240 patients infected with Gram-negative bacterial pneumonia to receive beta-lactam (meropenem, cefepime, or piperacillin/tazobactam) continuous or intermittent infusion and collect baseline and regular follow-up respiratory cultures to assess the development of new resistance. The investigators will measure beta-lactam concentration to assess the impact of drug exposure on the bacterial resistance.


Eligibility criteria: Inclusion Criteria:

* Admission to the ICU with severe pneumonia (IDSA/ATS 2016/2019): presence of signs, symptoms and confirmatory chest imaging consistent with pneumonia (e.g. fever, cough and pulmonary infiltrate by chest radiograph)
* Age ≥18 years
* Positive respiratory culture (with or without an initial positive rapid identification test and/or Gram stain) for Gram-negative bacteria including, but not limited to, P. aeruginosa, K. pneumoniae, E. coli, S. marcescens, H. influenzae, Enterobacter spp., M. catarrhalis, A. baumannii, Achromobacter spp., P. mirabilis, and/or B. cepacia
* Received within the last 72 hours or will receive meropenem, cefepime, or piperacillin/tazobactam therapy

Exclusion Criteria:

* Pregnancy
* Prisoners
* Allergy to the beta-lactams to be administered in this study
* On renal replacement therapy at the time of randomization
* Baseline culture resistant to the beta-lactams in the study
* COVID patients enrolled in other trials

Primary outcomes:
measure: Gram-negative Bacterial Resistance Emergence Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
timeFrame: 4 weeks
Secondary outcomes:
measure: Superinfection Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens.
timeFrame: 4 weeks
measure: Microbiologic Eradication Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
timeFrame: 4 weeks
measure: Clinical Cure at Day 7 of Therapy Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
timeFrame: 7 Days
measure: Clinical Cure at the End of Therapy Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
timeFrame: 4 weeks
measure: Mortality Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
timeFrame: 4 weeks
measure: Hospital Length of Stay Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens.
timeFrame: 4 weeks (may extend beyond depending on patient length of stay in hospital)
measure: Intensive Care Unit (ICU) Length of Stay Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
timeFrame: 4 weeks (may extend beyond depending on patient length of stay in ICU)
measure: Percent of Time Free Drug Concentrations Remain Above the Minimum Inhibitory Concentration (%fT>MIC) in the Dosing Interval Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
timeFrame: 4 weeks
measure: Percent of Time Free Drug Concentrations Remain Above Four Multiples of the Minimum Inhibitory Concentration (%fT>4xMIC) in the Dosing Interval Between Patients Treated With Continuous and Intermittent Infusion Beta-lactam Regimens
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Charles Peloquin
role: PRINCIPAL_INVESTIGATOR
References: