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

17 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the antibiotic ceftolozane-tazobactam can effectively treat infections caused by Pseudomonas aeruginosa, a challenging bacteria. Participants will receive the treatment intravenously for 10-14 days. Suitable candidates include those with blood cancer or a history of stem cell transplant who have been diagnosed with a Pseudomonas aeruginosa infection, often associated with pneumonia. The trial seeks to evaluate if this treatment serves well as the primary antibiotic choice for these infections. Researchers will monitor participants for about 60 days to assess the treatment's effectiveness and any side effects. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's function in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking medical advancements.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that ceftolozane-tazobactam is generally safe and effective for treating infections caused by Pseudomonas aeruginosa. Previous studies found it to be a reliable choice. The FDA has approved this treatment for adults with certain serious bacterial infections, indicating a well-understood safety profile.

While specific information about its use in pregnant women is lacking, hospitals have used it without major issues for most patients. Most side effects are mild or moderate, such as nausea or diarrhea, and serious side effects are rare. Overall, ceftolozane-tazobactam appears to be a safe option for treating difficult bacterial infections. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Pseudomonas infections?

Unlike the standard antibiotics used to treat Pseudomonas infections, which often include drugs like ciprofloxacin or piperacillin-tazobactam, ceftolozane-tazobactam offers a new combination of active ingredients specifically designed to tackle resistant strains. This treatment is unique because it combines ceftolozane, a cephalosporin antibiotic, with tazobactam, a beta-lactamase inhibitor, enhancing its ability to overcome bacterial defenses. Researchers are excited about this treatment because it has shown promise in fighting infections that don't respond well to conventional antibiotics. Additionally, its targeted mechanism may lead to better outcomes with fewer side effects.

What is the effectiveness track record for ceftolozane-tazobactam in treating Pseudomonas infections?

Research has shown that the drug ceftolozane-tazobactam, which participants in this trial will receive, effectively treats infections caused by the bacteria Pseudomonas aeruginosa. One study successfully treated 71% of patients with strains resistant to multiple drugs, including many with pneumonia. Another study found a 61% success rate in patients treated with this drug. These results suggest that ceftolozane-tazobactam could be a promising option for combating challenging bacterial infections like those caused by Pseudomonas aeruginosa. ^{4 6 7 8 9}

Who Is on the Research Team?

Markus Plate, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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 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 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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5848332/

Ceftolozane-Tazobactam for the Treatment of Multidrug ... In this small study, ceftolozane-tazobactam was successful in treating 71% of patients with MDR-P. aeruginosa infections, most of whom had pneumonia. The ...

2. thelancet.com thelancet.com/journals/laninf/article/PIIS1473-3099(24)00648-0/abstract

Effectiveness of ceftazidime–avibactam versus ceftolozane ... Clinical success was observed in 128 (61%) of 210 patients treated with ceftolozane–tazobactam and 109 (52%) of 210 patients treated with ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2213716525001468

Real-world analysis of ceftolozane/tazobactam prescribing ... This study focuses on chronic pulmonary disease (CPD) and respiratory-related infections (RRI), including pneumonia, from SPECTRA study.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38252038/

Perspectives on the use of ceftolozane/tazobactam In this article, we review the clinical trial evidence and key real-world effectiveness data of ceftolozane/tazobactam for the treatment of ...

5. academic.oup.com academic.oup.com/ofid/article/11/2/ofae037/7612589

Ceftolozane/Tazobactam for the Treatment of Complicated ... Complete or partial cure was achieved in 71.7% of patients, C/T was discontinued upon adaptation to microbiology results in 11.3% of patients ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7000837/

Clinical and Safety Evaluation of Continuously Infused ... Conclusions. Ceftolozane/tazobactam delivered as a continuous infusion may be a safe, effective, and convenient way to treat infections caused by P aeruginosa.

7. merck.com merck.com/product/usa/pi_circulars/z/zerbaxa/zerbaxa_pi.pdf

zerbaxa_pi.pdf There are no data available on ZERBAXA, ceftolozane or tazobactam use in pregnant women to allow assessment of a drug-associated risk of major birth defects ...

8. tandfonline.com tandfonline.com/doi/full/10.2217/fmb-2023-0197

Perspectives on the use of ceftolozane/tazobactam Characteristics and outcomes of complicated intra-abdominal infections involving Pseudomonas aeruginosa from a randomized, double-blind, phase 3 ceftolozane- ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/206829s011s012lbl.pdf

ZERBAXA (ceftolozane and tazobactam) - accessdata.fda.gov ZERBAXA is indicated for the treatment of adult patients (18 years and older) with hospital-acquired bacterial pneumonia and ventilator-associated bacterial ...