Ceftolozane-Tazobactam for Directed Treatment of Pseudomonas Aeruginosa Bacteremia and Pneumonia in Patients With Hematological Malignancies and Hematopoietic Stem Cell Transplantation

Phase 4TerminatedNCT04673175

Weill Medical College of Cornell University17 enrolled

Overview

The goal of this clinical trial is to learn whether the antibiotic ceftolozane-tazobactam works to treat serious Pseudomonas aeruginosa infections in people with blood cancers or who received a stem cell transplant. The main question it aims to answer is whether participants reach clinical success 30 days after the infection is first found. Clinical success means the person is alive, their infection symptoms are improving, and the infection has not returned. Participants will receive ceftolozane-tazobactam through a vein every 8 hours for 10 to 14 days. Treatment may continue for up to 21 days if the infection is not improving or keeps coming back. The infection is diagnosed using the hospital's standard rapid molecular tests, which help confirm Pseudomonas aeruginosa quickly so treatment can begin right away. Researchers will follow participants during their hospital stay and check on them around 30 and 60 days to see how well the treatment worked. The study will also look at how long it takes for the infection to clear, how long participants stay in the hospital or intensive care unit, and whether the bacteria become resistant to antibiotics. In addition to the prospective ceftolozane-tazobactam group, the study includes a historical control group made up of patients with similar infections who were treated in the past with standard anti-pseudomonal antibiotics (such as cefepime, ceftazidime, piperacillin-tazobactam, or meropenem). Data from these historical controls are collected by chart review and analyzed alongside the prospective group to compare outcomes. Historical controls do not receive study-directed treatment and are not actively enrolled under this protocol.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Eligibility Criteria Inclusion Criteria * Presence of a hematologic malignancy or a history of hematopoietic stem cell transplantation * Identification of Pseudomonas aeruginosa by rapid molecular diagnostic testing from a positive blood culture or from a respiratory sample in the setting of radiologically documented pneumonia with compatible clinical symptoms * Age 18 years or older * Ability of the participant or legally authorized representative to provide informed consent Exclusion Criteria * Receipt of more than 72 hours of non-study anti pseudomonal therapy for the infection being treated * Known anaphylactic hypersensitivity or allergic reaction to cephalosporins * History of a Pseudomonas aeruginosa isolate with a ceftolozane or tazobactam MIC greater than 4 micrograms per milliliter * Polymicrobial aerobic Gram negative infection, as determined by the infectious diseases research team * Hemodialysis, continuous renal replacement therapy, or creatinine clearance less than 15 milliliters per minute * Expected mortality within 48 hours of screening Eligibility Criteria for Historical Controls Inclusion Criteria * Presence of a hematologic malignancy or a history of hematopoietic stem cell transplantation * Identification of Pseudomonas aeruginosa associated with bacteremia and or pneumonia * Age 18 years or older * Survival greater than 48 hours after initiation of anti pseudomonal therapy for Pseudomonas aeruginosa bacteremia and or pneumonia Exclusion Criteria * Known anaphylactic hypersensitivity or allergic reaction to cephalosporins * History of a Pseudomonas aeruginosa isolate with a ceftolozane or tazobactam MIC greater than 4 micrograms per milliliter * Polymicrobial aerobic Gram negative infection, as determined by the infectious diseases research team * Hemodialysis, continuous renal replacement therapy, or creatinine clearance less than 15 milliliters per minute

Outcomes

Primary Outcomes

Clinical Success at Day 30

Clinical success 30 days after collection of the index culture. Clinical success is defined as meeting all of the following criteria at that time point: survival; resolution or near resolution of baseline clinical manifestations, including fever, hypoxia, and signs or symptoms of sepsis; and absence of recurrent infection due to Pseudomonas aeruginosa or persistent infection despite more than 7 days of anti-pseudomonal therapy.

Time frame: 30 days after collection of the index culture

Secondary Outcomes

Survival at Day 30

Survival status 30 days after initiation of anti-pseudomonal therapy for the index infection, assessed by chart review or phone contact.

Time frame: 30 days after initiation of anti-pseudomonal therapy for the index infection

Survival at Day 60

Survival status 60 days after initiation of anti-pseudomonal therapy for the index infection, assessed by chart review or phone contact.

Time frame: 60 days after initiation of anti-pseudomonal therapy for the index infection

Time to Resolution of Bacteremia

Time (days) from the index positive blood culture for Pseudomonas aeruginosa to bacteremia resolution. Resolution was defined as the date of the first of two consecutive negative blood cultures obtained after the index culture. Participants without follow-up blood cultures were excluded from this analysis.

Time frame: From index culture collection up to 60 days

Length of Hospital Stay

Total number of days hospitalized for the admission during which the index Pseudomonas aeruginosa infection is treated, measured beginning on the date of index culture collection and obtained from the Hospitalization Status Assessment.

Time frame: From index culture collection through discharge from the hospital admission for the index infection (up to 60 days)

Emergence of Ceftolozane-tazobactam Resistant Isolates

Occurrence of Pseudomonas aeruginosa isolates that newly demonstrate resistance to ceftolozane-tazobactam on antimicrobial susceptibility testing after initiation of therapy for the index infection.

Time frame: From index culture collection up to 60 days

Time to Appropriate Therapy

Time (in hours) from index culture collection for the index Pseudomonas aeruginosa infection to initiation of an anti-pseudomonal agent deemed appropriate based on antimicrobial susceptibility results.

Time frame: From index culture collection up to 60 days

Resolution of Baseline Clinical Manifestations

Resolution or near resolution of baseline fever, hypoxia, or signs and symptoms of sepsis related to the index infection at 30 days after index culture collection, as assessed by physical examination findings and clinical documentation.

Time frame: 30 days after collection of the index culture

Modifications to Initial Antimicrobial Therapy

Number of participants with any modification to the initial study-directed anti-pseudomonal regimen for the index infection, defined as either (1) discontinuation of ceftolozane-tazobactam with switch to another anti-pseudomonal agent or (2) addition of another anti-pseudomonal antibiotic during the treatment course. Outpatient levofloxacin was not considered a modification.

Time frame: From initiation of study ceftolozane-tazobactam therapy through end of study-directed anti-pseudomonal treatment (up to 21 days)

Emergence of Other Bacteria During Therapy

Identification of new bacterial pathogens identified in blood cultures during study-directed ceftolozane-tazobactam treatment for the index infection.

Time frame: From initiation of study ceftolozane-tazobactam therapy through end of ceftolozane-tazobactam treatment (up to 21 days)

Number of Days on Ventilator

Total number of days requiring invasive mechanical ventilation during the index admission, measured beginning on the date of index culture collection and abstracted from the medical record.

Time frame: From index culture collection through discharge from the hospital admission for the index infection (up to 60 days)

ICU Length of Stay

Total number of days spent in an intensive care unit during the index admission, measured beginning on the date of index culture collection and obtained from the Hospitalization Status Assessment.

Time frame: From index culture collection through discharge from the hospital admission for the index infection (up to 60 days)

Ceftolozane-Tazobactam for Directed Treatment of Pseudomonas Aeruginosa Bacteremia and Pneumonia in Patients With Hematological Malignancies and Hematopoietic Stem Cell Transplantation

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes