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

Study Overview
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Brief Summary
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This is an open-label study, where participants will be given ceftolozane-tazobactam as the primary treatment for Pseudomonas aeruginosa infections. Open-label means both the investigator and the participant will known what drug will be given. Participants will be followed for approximately 60 days. Ceftolozane-tazobactam is approved by the Food and Drug Administration (FDA) for treatment of serious bacterial infection and the investigator hypothesizes that ceftolozane/tazobactam may be effective as the primary antibiotic treatment for Pseudomonas aeruginosa infections.

Official Title
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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

Conditions
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Pseudomonas Aeruginosa, Pneumonia, Hematologic Malignancy

Intervention / Treatment
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* Drug: Ceftolozane / Tazobactam Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years old Presence of hematologic malignancy or Hematopoietic Stem Cell Transplantation Exclusion Criteria: Under the age of 18 years old Anaphylactic hypersensitivity or allergic reaction to cephalosporins Participants with expected mortality within 48 hours Hemodialysis or continuous renal replacement therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ceftolozane-Tazobactam<br>Participants receive ceftolozane-tazobactam by injection directly into the vein (intravenously, IV) every 8 hours for 10-14 days. | Drug: Ceftolozane / Tazobactam Injection<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global response at end of therapy | The proportion of subjects with a complete or partial Global Response (GR). Complete response is defined as Survival within the prespecified period of observation, resolution of all attributable symptoms and signs of disease and radiological abnormalities, and microbiological evidence of eradication of disease. Partial response is defined as Survival within the prespecified period of observation, improvement in attributable symptoms and signs of disease and radiological abnormalities, and evidence of clearance of cultures. | Day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at 30 days | Survival will be assessed by chart review or phone visit, as appropriate. | Day 30 | 
| Survival at 60 days | Survival will be assessed by chart review or phone visit, as appropriate. | Day 60 | 
| Time in days to resolution of bacteremia | This will be measured in days from the Subject's initial Pseudomonas aeruginosa blood culture, until the subject has two consecutive negative blood cultures for Pseudomonas aeruginosa , assessed by examining results from daily blood cultures obtained as standard of care. | Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28 | 
| Time in days of hospital stays | This will be obtained from Hospitalization Status Assessment. | Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 30, Day 60 | 
| Time in days of ICU stays | This will be obtained from Hospitalization Status Assessment. | Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 30, Day 60 | 
| Time in days to emergence of resistant isolates | This will be measured in days from the most recent microbiological isolate susceptibility testing to ceftolozane/tazobactam showing no resistance, to the first identification of resistance to ceftolozane/tazobactam. | Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28 | 
| Time in days to appropriate therapy | This will be measured in days from initial treatment for Pseudomonas aeruginosa infection until the Subject begins therapy for this infection that is efficacious, based on microbiologic isolate susceptibility testing and review of Subject's concomitant medications. | Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 30, Day 60 | 
| Change of microbiological eradication | Microbiological eradication will be defined by resolution of positive blood cultures, by repeat assessment of bronchoalveolar lavage, or in the absence of repeat respiratory tract specimen. | Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28 | 
| Incidence of abnormal and physical examinations findings - general appearance | A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted. | 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) | 
| Incidence of abnormal and physical examinations findings - neurological | A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted. | 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) | 
| Incidence of abnormal and physical examinations findings - heart/cardiovascular | A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted. | 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) | 
| Incidence of abnormal and physical examinations findings - lungs | A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted. | 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) | 
| Incidence of abnormal and physical examinations findings - abdomen | A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted. | 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) | 
| Incidence of abnormal and physical examinations findings - endocrine | A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted. | 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) | 
| Incidence of abnormal and physical examinations findings - extremities | A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted. | 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) | 
| Incidence of abnormal and physical examinations findings - lymphatic | A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted. | 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) | 
| Incidence of abnormal and physical examinations findings - skin | A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted. | 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) | 
| Time in days until stabilization or resolution of pneumonic infiltrates | This will be measured in days from Subject's initial presentation of pneumonic infiltrates until Subject's pneumonic infiltrates stabilize or resolve, based on diagnostic imaging obtained as standard of care. | Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28 | 
| Time in days to initial antimicrobial therapy | This will be measured in days from initial diagnosis of Pseudomonas aeruginosa infection unit initiation of antimicrobial therapy for this infection, based on review of Subject's concomitant medications. | Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 30, Day 60 | 
| Change in days until emergence of other bacteria | This will be measured in days from initial diagnosis of Pseudomonas aeruginosa infection until identification of additional bacteria, assessed by examining results from daily blood cultures obtained as standard of care. | Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28 | 
| Number of days on ventilator, as measured by assessment of clinical status |  | Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pseudomonas Aeruginosa, Pneumonia, Hematologic Malignancy, Ceftolozane-Tazobactam, Zerbaxa