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

A Pilot Study of Ceftolozane-Tazobactam in Conjunction With Rapid Molecular Diagnosis for Directed Treatment of Pseudomonas Aeruginosa Bacteremia and Pneumonia in Patients With Hematological Malignancies and Hematopoietic Stem Cell Transplantation

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.

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