Bacteremia, Hematologic Malignancy, Hematopoietic Stem Cell Transplant (HSCT), Pneumonia, Pseudomonas Aeruginosa Infection
Conditions
Keywords
Pseudomonas Aeruginosa, Pneumonia, Hematologic Malignancy, Ceftolozane-Tazobactam, Zerbaxa, Stem Cell Transplant Recipients, Immunocompromised Hosts, Gram-Negative Bacterial Infections
Brief summary
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.
Interventions
DRUGCeftolozane / Tazobactam Injection
Zerbaxa (ceftolozane/tazobactam) for injection is supplied as a white to yellow sterile powder for reconstitution in single-use vials; each vial contains 1 g ceftolozane (equivalent to 1.147 g of ceftolozane sulfate) and 0.5 g tazobactam (equivalent to 0.537 g of tazobactam sodium).
Sponsors
Weill Medical College of Cornell University
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study. No parties are masked.
Intervention model description
The study includes two groups analyzed in parallel: (1) a prospective treatment arm in which participants receive ceftolozane-tazobactam for Pseudomonas aeruginosa infection, and (2) a historical control arm consisting of patients previously treated with standard-of-care anti-pseudomonal therapy. Historical controls are identified retrospectively and are not prospectively assigned or treated under this protocol.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Success at Day 30 | 30 days after collection of the index culture | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival at Day 30 | 30 days after initiation of anti-pseudomonal therapy for the index infection | Survival status 30 days after initiation of anti-pseudomonal therapy for the index infection, assessed by chart review or phone contact. |
| Survival at Day 60 | 60 days after initiation of anti-pseudomonal therapy for the index infection | Survival status 60 days after initiation of anti-pseudomonal therapy for the index infection, assessed by chart review or phone contact. |
| Time to Resolution of Bacteremia | From index culture collection up to 60 days | 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. |
| Length of Hospital Stay | From index culture collection through discharge from the hospital admission for the index infection (up to 60 days) | 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. |
| Emergence of Ceftolozane-tazobactam Resistant Isolates | From index culture collection up to 60 days | 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 to Appropriate Therapy | From index culture collection up to 60 days | 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. |
| Resolution of Baseline Clinical Manifestations | 30 days after collection of the index culture | 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. |
| Modifications to Initial Antimicrobial Therapy | From initiation of study ceftolozane-tazobactam therapy through end of study-directed anti-pseudomonal treatment (up to 21 days) | 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. |
| Emergence of Other Bacteria During Therapy | From initiation of study ceftolozane-tazobactam therapy through end of ceftolozane-tazobactam treatment (up to 21 days) | Identification of new bacterial pathogens identified in blood cultures during study-directed ceftolozane-tazobactam treatment for the index infection. |
| Number of Days on Ventilator | From index culture collection through discharge from the hospital admission for the index infection (up to 60 days) | 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. |
| ICU Length of Stay | From index culture collection through discharge from the hospital admission for the index infection (up to 60 days) | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMarkus Plate, MD
Weill Medical College of Cornell University
Participant flow
Recruitment details
Prospective participants for the ceftolozane-tazobactam arm were recruited at a single academic tertiary care hospital among adults with hematologic malignancies or hematopoietic stem cell transplant and documented Pseudomonas aeruginosa bacteremia or pneumonia between January 2023 and February 2025. Historical controls were identified retrospectively from the same institution.
Pre-assignment details
A total of 17 consent events occurred among 16 unique participants. Per protocol, one participant was eligible for re-enrollment after developing a separate Pseudomonas aeruginosa infection and received study treatment during both enrollments. For statistical analyses, this participant was counted once to avoid bias. Analyses therefore summarize outcomes for 16 unique treated participants.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age-adjusted Charlson Comorbidity Index | 5 score on a scale |
| Age, Continuous | 67 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Hematologic Malignancy Type Acute lymphoblastic leukemia | 4 Participants |
| Hematologic Malignancy Type Acute myeloid leukemia | 8 Participants |
| Hematologic Malignancy Type Chronic leukemia | 6 Participants |
| Hematologic Malignancy Type Multiple myeloma | 7 Participants |
| Hematologic Malignancy Type Myelodysplastic Syndromes | 4 Participants |
| Hematologic Malignancy Type Non-Hodgkin's lymphoma | 3 Participants |
| Hematopoietic cell transplant recipient No | 36 Participants |
| Hematopoietic cell transplant recipient Yes | 18 Participants |
| Infection Type at Index Pseudomonas Infection Bacteremia | 52 Participants |
| Infection Type at Index Pseudomonas Infection Pneumonia | 12 Participants |
| Neutropenia Status at Index Pseudomonas Infection Neutropenic | 28 Participants |
| Neutropenia Status at Index Pseudomonas Infection Not Neutropenic | 9 Participants |
| Pitt Bacteremia Score | 1 score on a scale |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants |
| Race/Ethnicity, Customized Race Decline to answer | 0 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Race Other combinations not described | 0 Participants |
| Race/Ethnicity, Customized Race White | 14 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 16 | 20 / 48 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 5 / 16 | 0 / 0 |
Outcome results
None listed