Ceftolozane-Tazobactam for Pseudomonas Infections

Overseen By Elizabeth Salsgiver, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Weill Medical College of Cornell University

Disqualifiers: Allergy to cephalosporins, Renal failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug Ceftolozane-Tazobactam for Pseudomonas infections?

Research shows that Ceftolozane-Tazobactam is effective against Pseudomonas aeruginosa, including drug-resistant strains. In a study of patients with complicated intra-abdominal infections, it achieved a 100% clinical cure rate in those evaluated, supporting its use for such infections. ^{1 2 3 4 5}

Is Ceftolozane-Tazobactam generally safe for humans?

Ceftolozane-Tazobactam has been studied for safety in treating infections caused by drug-resistant Pseudomonas aeruginosa, and it did not show significant differences in safety compared to another treatment option, Ceftazidime-Avibactam, in a study involving 200 patients. It is also approved for treating certain infections in adults, suggesting it is generally considered safe for human use. ^{1 3 6 7 8}

How is the drug Ceftolozane/Tazobactam unique for treating Pseudomonas infections?

Ceftolozane/Tazobactam is unique because it is a combination of a novel cephalosporin (a type of antibiotic) and a beta-lactamase inhibitor, which helps it remain effective against drug-resistant Pseudomonas aeruginosa, a challenging bacteria to treat. This makes it a potentially important option when other treatments fail, especially for infections that are resistant to many other antibiotics. ^{1 3 7 9 10}

Research Team

Markus Plate, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for adults over 18 with blood cancers or who've had a stem cell transplant and are now facing Pseudomonas aeruginosa infections. It's not suitable for those under 18, expected to die within 48 hours, on kidney dialysis treatments, or allergic to cephalosporin antibiotics.

Inclusion Criteria

I am 18 years old or older.

I have a blood cancer or have had a stem cell transplant.

Exclusion Criteria

I am on hemodialysis or continuous renal replacement therapy.

You are expected to pass away within the next 48 hours.

I am under 18 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive ceftolozane-tazobactam intravenously every 8 hours for 10-14 days

2 weeks

Daily visits for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 days

Regular monitoring through chart review or phone visits

Treatment Details

Interventions

• Ceftolozane / Tazobactam Injection

Trial Overview The study tests Ceftolozane-Tazobactam injections as the main treatment for certain serious bacterial infections in patients with hematological conditions. Everyone knows what treatment they're getting (open-label), and they'll be watched over for about two months.

Participant Groups

Group I: Ceftolozane-Tazobactam Experimental Treatment 1 Intervention

Participants receive ceftolozane-tazobactam by injection directly into the vein (intravenously, IV) every 8 hours for 10-14 days.

Ceftolozane / Tazobactam Injection is already approved in United States, European Union for the following indications:

Approved in United States as Zerbaxa for:

• Complicated intra-abdominal infections
• Acute pyelonephritis
• Complicated urinary tract infections
• Hospital-acquired bacterial pneumonia and Ventilator-associated bacterial pneumonia (HABP/VABP)

Approved in European Union as Zerbaxa for:

• Complicated intra-abdominal infections
• Acute pyelonephritis
• Complicated urinary tract infections
• Hospital-acquired bacterial pneumonia and Ventilator-associated bacterial pneumonia (HABP/VABP)

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a study of 200 patients with drug-resistant Pseudomonas aeruginosa infections, ceftolozane/tazobactam was found to be significantly more effective in achieving clinical cure compared to polymyxins or aminoglycosides, with an adjusted odds ratio of 2.63.

Ceftolozane/tazobactam also demonstrated a protective effect against acute kidney injury (AKI), with an adjusted odds ratio of 0.08, indicating a lower risk of kidney damage compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftolozane/Tazobactam vs Polymyxin or Aminoglycoside-based Regimens for the Treatment of Drug-resistant Pseudomonas aeruginosa. Pogue, JM., Kaye, KS., Veve, MP., et al.[2021]

The study identified that the same XDR Pseudomonas aeruginosa clone developed resistance to ceftolozane/tazobactam and ceftazidime/avibactam during treatment, primarily through mutations in the OXA-10 enzyme, which enhanced resistance to these antibiotics.

Despite the development of resistance to cephalosporins, imipenem/relebactam remained effective against all strains, suggesting it could be a viable treatment option for infections caused by resistant P. aeruginosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular mechanisms driving the in vivo development of OXA-10-mediated resistance to ceftolozane/tazobactam and ceftazidime/avibactam during treatment of XDR Pseudomonas aeruginosa infections. Arca-Suárez, J., Lasarte-Monterrubio, C., Rodiño-Janeiro, BK., et al.[2021]

Ceftolozane/tazobactam showed remarkable effectiveness against Pseudomonas aeruginosa, with 98.3% of clinical isolates testing susceptible, making it the most active antimicrobial in the study of 3229 isolates collected across Canada from 2008 to 2016.

The combination was particularly effective against multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, with 90.5% of MDR and 78.6% of XDR isolates remaining susceptible, suggesting its potential as a treatment option for difficult-to-treat infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro activity of ceftolozane/tazobactam versus antimicrobial non-susceptible Pseudomonas aeruginosa clinical isolates including MDR and XDR isolates obtained from across Canada as part of the CANWARD study, 2008-16. Walkty, A., Adam, H., Baxter, M., et al.[2019]

Ceftolozane-tazobactam is effective against Pseudomonas aeruginosa, including resistant strains, making it a valuable treatment option for infections caused by this bacteria.

Resistance to ceftolozane-tazobactam was identified in a patient after 6 weeks of treatment, caused by a single mutation in the AmpC enzyme, highlighting the potential for resistance development even with effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergence of Ceftolozane-Tazobactam-Resistant Pseudomonas aeruginosa during Treatment Is Mediated by a Single AmpC Structural Mutation. MacVane, SH., Pandey, R., Steed, LL., et al.[2018]

Ceftolozane-tazobactam showed excellent effectiveness against multidrug-resistant Pseudomonas aeruginosa in patients with complicated intra-abdominal infections, achieving a clinical cure rate of 100% in those treated with this combination therapy.

In comparison, meropenem had a slightly lower clinical cure rate of 93.1%, suggesting that ceftolozane-tazobactam may be a superior option for treating infections caused by this resistant pathogen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and Outcomes of Complicated Intra-abdominal Infections Involving Pseudomonas aeruginosa from a Randomized, Double-Blind, Phase 3 Ceftolozane-Tazobactam Study. Miller, B., Popejoy, MW., Hershberger, E., et al.[2018]

In a study of 200 patients with multidrug-resistant Pseudomonas aeruginosa infections, ceftolozane-tazobactam (C-T) and ceftazidime-avibactam (CAZ-AVI) showed no significant differences in overall in-hospital mortality (44% for C-T vs. 37% for CAZ-AVI) or 30-day mortality rates (27% vs. 23%).

Both C-T and CAZ-AVI demonstrated similar clinical cure rates (61% for C-T vs. 66% for CAZ-AVI) and safety profiles, indicating that either drug can be effectively used for treating these challenging infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftolozane-Tazobactam Versus Ceftazidime-Avibactam for the Treatment of Infections Caused by Multidrug-Resistant Pseudomonas aeruginosa: a Multicenter Cohort Study. Almangour, TA., Ghonem, L., Alassiri, D., et al.[2023]

Ceftolozane-tazobactam is a new antibiotic combination approved for treating complicated infections in adults, showing strong effectiveness against Pseudomonas aeruginosa, a common pathogen in cystic fibrosis.

This medication may be a valuable treatment option for children with cystic fibrosis experiencing exacerbations due to Pseudomonas aeruginosa, especially when other treatments have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftolozane/Tazobactam for Treating Children With Exacerbations of Cystic Fibrosis Due to Pseudomonas aeruginosa: A Review of Available Data. Garazzino, S., Altieri, E., Silvestro, E., et al.[2020]

Ceftolozane-tazobactam was safely and effectively used to treat a 79-year-old patient with multidrug-resistant Pseudomonas aeruginosa pneumonia, despite his end-stage renal disease and ongoing hemodialysis.

The treatment regimen included a loading dose of 1.5 g followed by 300 mg every 8 hours for 13 days, with no adverse events reported, indicating its potential as a viable option for similar patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftolozane-tazobactam for the treatment of multidrug-resistant Pseudomonas aeruginosa pneumonia in a patient receiving intermittent hemodialysis. Alessa, MA., Almangour, TA., Alhossan, A., et al.[2019]

Ceftolozane/tazobactam shows potential effectiveness against multidrug-resistant Pseudomonas aeruginosa, with 30% of isolates from cystic fibrosis patients being susceptible to the antibiotic.

In a study of 30 samples from 23 adult cystic fibrosis patients, 57% of the Pseudomonas isolates were resistant, indicating that while ceftolozane/tazobactam may be beneficial, its use should be carefully considered based on susceptibility testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftolozane/tazobactam sensitivity patterns in Pseudomonas aeruginosa isolates recovered from sputum of cystic fibrosis patients. Finklea, JD., Hollaway, R., Lowe, K., et al.[2018]

Ceftolozane/tazobactam was found to be the most effective β-lactam antibiotic against Pseudomonas aeruginosa, inhibiting 91% of isolates at a low concentration (MIC ≤4 mg/L) in a study involving 2038 Gram-negative organisms from 11 medical centers in Asia.

The drug also showed strong activity against Enterobacterales, particularly against strains that are not resistant to carbapenems, making it a promising option for treating infections caused by these bacteria, although it was ineffective against carbapenem-resistant strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftolozane/Tazobactam Activity Against Drug-Resistant Pseudomonas aeruginosa and Enterobacterales Causing Healthcare-Associated Infections in Eight Asian Countries: Report from an Antimicrobial Surveillance Program (2016-2018). Pfaller, M., Shortridge, D., Chen, WT., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Ceftolozane/Tazobactam vs Polymyxin or Aminoglycoside-based Regimens for the Treatment of Drug-resistant Pseudomonas aeruginosa. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Molecular mechanisms driving the in vivo development of OXA-10-mediated resistance to ceftolozane/tazobactam and ceftazidime/avibactam during treatment of XDR Pseudomonas aeruginosa infections. [2021]

3. England pubmed.ncbi.nlm.nih.gov

In vitro activity of ceftolozane/tazobactam versus antimicrobial non-susceptible Pseudomonas aeruginosa clinical isolates including MDR and XDR isolates obtained from across Canada as part of the CANWARD study, 2008-16. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Emergence of Ceftolozane-Tazobactam-Resistant Pseudomonas aeruginosa during Treatment Is Mediated by a Single AmpC Structural Mutation. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Characteristics and Outcomes of Complicated Intra-abdominal Infections Involving Pseudomonas aeruginosa from a Randomized, Double-Blind, Phase 3 Ceftolozane-Tazobactam Study. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Ceftolozane-Tazobactam Versus Ceftazidime-Avibactam for the Treatment of Infections Caused by Multidrug-Resistant Pseudomonas aeruginosa: a Multicenter Cohort Study. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Ceftolozane/Tazobactam for Treating Children With Exacerbations of Cystic Fibrosis Due to Pseudomonas aeruginosa: A Review of Available Data. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Ceftolozane-tazobactam for the treatment of multidrug-resistant Pseudomonas aeruginosa pneumonia in a patient receiving intermittent hemodialysis. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Ceftolozane/tazobactam sensitivity patterns in Pseudomonas aeruginosa isolates recovered from sputum of cystic fibrosis patients. [2018]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Ceftolozane/Tazobactam Activity Against Drug-Resistant Pseudomonas aeruginosa and Enterobacterales Causing Healthcare-Associated Infections in Eight Asian Countries: Report from an Antimicrobial Surveillance Program (2016-2018). [2022]