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

NCT04673175 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: 19-11021048
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Pneumonia; Hematologic Malignancy; Pseudomonas Aeruginosa Infection; Bacteremia; Hematopoietic Stem Cell Transplant (HSCT)

Keywords

Pseudomonas Aeruginosa; Pneumonia; Hematologic Malignancy; Ceftolozane-Tazobactam; Zerbaxa; Stem Cell Transplant Recipients; Immunocompromised Hosts; Gram-Negative Bacterial Infections

Outcome Measures

Primary Outcomes (1)

• 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.

  30 days after collection of the index culture

Secondary Outcomes (11)

• Survival at Day 30

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

• Survival at Day 60

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

• Time to Resolution of Bacteremia

  From index culture collection up to 60 days

• Length of Hospital Stay

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

• Emergence of Ceftolozane-tazobactam Resistant Isolates

  From index culture collection up to 60 days

Study Arms (2)

Ceftolozane-Tazobactam (Prospective Treatment Arm)

EXPERIMENTAL

Participants prospectively enrolled in the study received ceftolozane-tazobactam intravenously every 8 hours for approximately 10 to 14 days, with treatment extended up to 21 days if infection persisted or recurred. Outcomes for this arm were assessed according to the protocol's primary and secondary endpoints.

Drug: Ceftolozane / Tazobactam Injection

Historical Control (Standard of Care Prior to Study)

NO INTERVENTION

This arm consists of historical control patients with documented Pseudomonas aeruginosa bacteremia and/or pneumonia who received standard-of-care antimicrobial therapy prior to initiation of this study. These patients were included retrospectively for comparative analyses of selected primary and secondary endpoints. No study interventions were administered to this arm.

Interventions

Ceftolozane / Tazobactam Injection DRUG

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).

Ceftolozane-Tazobactam (Prospective Treatment Arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Related Publications (7)

• Satlin MJ, Walsh TJ. Multidrug-resistant Enterobacteriaceae, Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus: Three major threats to hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2017 Dec;19(6):10.1111/tid.12762. doi: 10.1111/tid.12762. Epub 2017 Oct 25.

  PMID: 28815897 BACKGROUND

• Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011 Feb 15;52(4):e56-93. doi: 10.1093/cid/cir073.

  PMID: 21258094 BACKGROUND

• Nguyen L, Garcia J, Gruenberg K, MacDougall C. Multidrug-Resistant Pseudomonas Infections: Hard to Treat, But Hope on the Horizon? Curr Infect Dis Rep. 2018 Jun 6;20(8):23. doi: 10.1007/s11908-018-0629-6.

  PMID: 29876674 BACKGROUND

• Kaye KS, Pogue JM. Infections Caused by Resistant Gram-Negative Bacteria: Epidemiology and Management. Pharmacotherapy. 2015 Oct;35(10):949-62. doi: 10.1002/phar.1636.

  PMID: 26497481 BACKGROUND

• Munita JM, Aitken SL, Miller WR, Perez F, Rosa R, Shimose LA, Lichtenberger PN, Abbo LM, Jain R, Nigo M, Wanger A, Araos R, Tran TT, Adachi J, Rakita R, Shelburne S, Bonomo RA, Arias CA. Multicenter Evaluation of Ceftolozane/Tazobactam for Serious Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa. Clin Infect Dis. 2017 Jul 1;65(1):158-161. doi: 10.1093/cid/cix014.

  PMID: 28329350 BACKGROUND

• Gallagher JC, Satlin MJ, Elabor A, Saraiya N, McCreary EK, Molnar E, El-Beyrouty C, Jones BM, Dixit D, Heil EL, Claeys KC, Hiles J, Vyas NM, Bland CM, Suh J, Biason K, McCoy D, King MA, Richards L, Harrington N, Guo Y, Chaudhry S, Lu X, Yu D. Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections: A Multicenter Study. Open Forum Infect Dis. 2018 Oct 31;5(11):ofy280. doi: 10.1093/ofid/ofy280. eCollection 2018 Nov.

  PMID: 30488041 BACKGROUND

• Petraitis V, Petraitiene R, Naing E, Aung T, Thi WP, Kavaliauskas P, Win Maung BB, Michel AO, Ricart Arbona RJ, DeRyke AC, Culshaw DL, Nicolau DP, Satlin MJ, Walsh TJ. Ceftolozane-Tazobactam in the Treatment of Experimental Pseudomonas aeruginosa Pneumonia in Persistently Neutropenic Rabbits: Impact on Strains with Genetically Defined Mechanisms of Resistance. Antimicrob Agents Chemother. 2019 Aug 23;63(9):e00344-19. doi: 10.1128/AAC.00344-19. Print 2019 Sep.

  PMID: 31235620 BACKGROUND

MeSH Terms

Conditions

Pneumonia; Hematologic Neoplasms; Pseudomonas Infections; Bacteremia; Gram-Negative Bacterial Infections

Interventions

ceftolozane, tazobactam drug combination

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Limitations of this study include the lack of randomization between patients that received ceftolozane-tazobactam and alternative therapies, which creates the potential for confounding. Also, the modest sample size limited the statistical power to detect difference between groups.

Results Point of Contact

• Title: Markus Plate, MD
• Organization: Weill Cornell Medicine

map9313@med.cornell.edu

212-746-7587

Study Officials

• Markus Plate, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study. No parties are masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 4, 2020
• First Posted: December 17, 2020
• Study Start: January 10, 2023
• Primary Completion: March 16, 2025
• Study Completion: March 16, 2025
• Last Updated: January 21, 2026
• Results First Posted: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)