UMIN-ICDS Clinical Trial
| Unique ID issued by UMIN | UMIN000062153 |
|---|---|
| Receipt number | R000070683 |
| Scientific Title | Effectiveness of Ceftolozane/Tazobactam Versus Polymyxins or Aminoglycosides for Multidrug-Resistant Pseudomonas aeruginosa Infections: A Systematic Review and Meta-Analysis |
| Date of disclosure of the study information | 2026/07/07 |
| Last modified on | 2026/07/07 08:42:19 |
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Basic information
Public title
Effectiveness of Ceftolozane/Tazobactam Versus Polymyxins or Aminoglycosides for Multidrug-Resistant Pseudomonas aeruginosa Infections: A Systematic Review and Meta-Analysis
Acronym
Effectiveness of Ceftolozane/Tazobactam Versus Polymyxins or Aminoglycosides for Multidrug-Resistant Pseudomonas aeruginosa Infections: A Systematic Review and Meta-Analysis
Scientific Title
Effectiveness of Ceftolozane/Tazobactam Versus Polymyxins or Aminoglycosides for Multidrug-Resistant Pseudomonas aeruginosa Infections: A Systematic Review and Meta-Analysis
Scientific Title:Acronym
Effectiveness of Ceftolozane/Tazobactam Versus Polymyxins or Aminoglycosides for Multidrug-Resistant Pseudomonas aeruginosa Infections: A Systematic Review and Meta-Analysis
Region
| Japan |
Condition
Condition
Multidrug-resistant (MDR), extensively drug-resistant (XDR), or difficult-to-treat resistance (DTR) Pseudomonas aeruginosa infections
Classification by specialty
| Infectious disease | Adult |
Classification by malignancy
Others
Genomic information
NO
Objectives
Narrative objectives1
Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are serious public health problems. Therefore, establishing effective therapeutic strategies is necessary. Historically, polymyxins and aminoglycosides were used for treatment; however, a major side effect is nephrotoxicity, which remains a significant clinical problem. Recently, novel beta-lactam/beta-lactamase inhibitor combinations, including ceftolozane/tazobactam, can be used against MDR P. aeruginosa, and several studies were performed.A meta-analysis by Chi et al. reported the efficacy and lower risk of acute kidney injury (AKI) of ceftolozane/tazobactam compared with polymyxins or aminoglycosides for gram-negative infections. However, limitations included the inclusion of infections regardless of drug resistance, and various AKI definitions. After that, a network meta-analysis by Collings et al. against MDR P. aeruginosa demonstrated that ceftolozane/tazobactam significantly improved clinical cure and reduced mortality. However, that study focused only on efficacy endpoints and did not evaluate AKI outcomes.Regarded as an evolution of the concept of Acute Renal Failure (ARF), Acute Kidney Injury (AKI) was introduced by the ADQI working group in 2004 to capture earlier declines in renal function. Although standardized criteria were established, such as the RIFLE classification defined that year and its evolution into the KDIGO criteria in 2012, past clinical studies often relied on inconsistent AKI definitions, resulting in a lack of robust evaluation.To overcome these limitations, we performed a systematic review and meta-analysis of literature published up to May 2026. By limiting criteria to studies on MDR P. aeruginosa infections that concurrently reported mortality and AKI incidence, we aimed to evaluate the efficacy and safety of ceftolozane/tazobactam-based therapy versus polymyxin- or aminoglycoside-based regimens.
Basic objectives2
Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase
Assessment
Primary outcomes
1. All-cause mortality
2. Incident rate of acute kidney injury
Key secondary outcomes
Base
Study type
Others,meta-analysis etc
Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment
Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10
Eligibility
Age-lower limit
| 18 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
Studies were eligible for inclusion if they evaluated hospitalized adult patients with multidrug-resistant Pseudomonas aeruginosa infection and compared ceftolozane/tazobactam-based therapy directly against polymyxin- or aminoglycoside-based regimens. Eligible studies were required to report both all-cause mortality and the incidence of acute kidney injury (AKI). For investigations evaluated a broader cohort receiving various novel cephems or other agents, inclusion was restricted to those from which data specific to the ceftolozane/tazobactam cohort could be isolated. Relevant literature was retrieved from major databases, including PubMed, Web of Science, and the Cochrane Library, without language restrictions.
Key exclusion criteria
Under 18 years old
Pregnancy
Inability to isolate MDR data (e.g., non-MDR P. aeruginosa or Enterobacterales predominant)
Missing primary outcomes (all-cause mortality or AKI incidence)
Incomplete full-text/data (letters, reviews, or conference abstracts only)
Target sample size
8
Research contact person
Name of lead principal investigator
| 1st name | Haruka |
| Middle name | |
| Last name | Imai |
Organization
Tohoku Medical and Pharmaceutical University and Tohoku Medical and Pharmaceutical University Hospital
Division name
Division of Infectious Diseases and Infection Control, Faculty of Medicine, and Division of Infectious Diseases and Department of Infection Prevention and Control
Zip code
983-8512
Address
1-12-1, Fukumuro, Miyagino-ku, Sendai, Miyagi, Japan
TEL
0222591221
m05009hi@jichi.ac.jp
Public contact
Name of contact person
| 1st name | Haruka |
| Middle name | |
| Last name | Imai |
Organization
Tohoku Medical and Pharmaceutical University and Tohoku Medical and Pharmaceutical University Hospit
Division name
Division of Infectious Diseases and Infection Control, Faculty of Medicine
Zip code
983-8512
Address
1-12-1, Fukumuro, Miyagino-ku, Sendai, Miyagi, Japan
TEL
0222591221
Homepage URL
m05009hi@jichi.ac.jp
Sponsor or person
Institute
Tohoku Medical and Pharmaceutical University
Institute
Department
Personal name
Funding Source
Organization
no organization
Organization
Division
Category of Funding Organization
Other
Nationality of Funding Organization
Other related organizations
Co-sponsor
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Tohoku Medical and Pharmaceutical University and Tohoku Medical and Pharmaceutical University Hospital
Address
1-12-1, Fukumuro, Miyagino-ku, Sendai, Miyagi, Japan
Tel
0222591221
m05009hi@jichi.ac.jp
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
Other administrative information
Date of disclosure of the study information
| 2026 | Year | 07 | Month | 07 | Day |
Related information
URL releasing protocol
Publication of results
Unpublished
Result
URL related to results and publications
Number of participants that the trial has enrolled
1387
Results
This meta-analysis compared outcomes of C/T versus comparators in 1,387 patients with MDRP infections. Pooling 8 retrospective cohorts, C/T was associated with lower mortality and reduced AKI risk. High heterogeneity and study design biases, particularly regarding baseline adjustment and lack of blinding, necessitate cautious interpretation of these findings.
Results date posted
| 2026 | Year | 07 | Month | 07 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Completed
Date of protocol fixation
| 2026 | Year | 06 | Month | 01 | Day |
Date of IRB
| 2026 | Year | 06 | Month | 01 | Day |
Anticipated trial start date
| 2026 | Year | 06 | Month | 01 | Day |
Last follow-up date
| 2026 | Year | 06 | Month | 01 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
| 2026 | Year | 07 | Month | 07 | Day |
Other
Other related information
The final meta-analysis included 8 studies with a total of 1,387 patients to evaluate mortality and acute kidney injury (AKI). However, in the study by Caffrey et al. (2022), the AKI analysis was limited to patients with available serum creatinine measurements at both baseline and follow-up (48 in the C/T group and 129 in the comparator group), resulting in a total of 1,352 patients included in the AKI analysis.
Management information
Registered date
| 2026 | Year | 07 | Month | 07 | Day |
Last modified on
| 2026 | Year | 07 | Month | 07 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000070683
