Cefiderocol plus ampicillin‑sulbactam versus colistin (with or without meropenem) for carbapenem‑resistant Acinetobacter infections
Cefiderocol and Ampicillin-sulbactam vs. Colistin or Colistin-meropenem for Carbapenem Resistant Acinetobacter Baumannii Bacteremia or Hospital-acquired Pneumonia: Controlled Clinical Study With Historical Controls (CASCADE)
This trial will test whether cefiderocol combined with ampicillin‑sulbactam works better than colistin (with or without meropenem) for adults with bloodstream infection or hospital/ventilator‑associated pneumonia caused by carbapenem‑resistant Acinetobacter baumannii.
Quick facts
| Phase | Phase 4 |
|---|---|
| Study type | Interventional |
| Enrollment | 734 (estimated) |
| Ages | 16 Years and up |
| Sex | All |
| Sponsor | Rambam Health Care Campus Academic / other |
| Locations | 3 sites (Haifa and 2 other locations) |
| Trial ID | NCT05922124 on ClinicalTrials.gov |
What this trial studies
This is a prospective, controlled cohort in which consecutive consenting adults with CRAB bloodstream infection, hospital‑acquired pneumonia, or ventilator‑associated pneumonia will receive cefiderocol plus ampicillin‑sulbactam at five hospitals in Israel and Italy. The planned CASCADE cohort of about 150 patients will be compared against historical CRAB patients from two recently completed randomized trials (AIDA and OVERCOME) that treated patients with colistin ± meropenem. Inclusion requires CRAB isolates susceptible to cefiderocol and limits prior effective therapy; polymicrobial carbapenem‑susceptible infections are excluded. Outcomes will be compared across cohorts to determine whether the cefiderocol combination yields better clinical results than the historical colistin‑based regimens.
Who should consider this trial
Good fit: Adults over 18 with CRAB bloodstream infection or hospital/ventilator‑associated pneumonia whose isolates are susceptible to cefiderocol and who have not had more than 72 hours of effective anti‑CRAB therapy prior to enrollment are ideal candidates.
Not a fit: Patients whose isolates are not susceptible to cefiderocol, those with clinically significant carbapenem‑susceptible co‑pathogens (polymicrobial infections), or those who have already received prolonged effective therapy are unlikely to benefit from enrollment.
Why it matters
Potential benefit: If successful, this regimen could provide a more effective and potentially less toxic treatment option for severe infections caused by carbapenem‑resistant A. baumannii.
How similar studies have performed: Prior randomized trials (AIDA and OVERCOME) found no advantage of colistin‑meropenem over colistin alone for CRAB, and prior experience with cefiderocol against Acinetobacter has been mixed with some analyses suggesting higher mortality, so the specific cefiderocol+ampicillin‑sulbactam combination remains relatively novel and not yet proven.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: Adults \>18 years with bacteremia or hospital-acquired pneumonia (HAP)/ ventilator-associated pneumonia (VAP) (Table 3) caused by carbapenem-resistant A. baumannii (CRAB) (meropenem and/ or imipenem minimal inhibitory concentration (MIC) \>8 μg/mL) susceptible to cefiderocol (disc zone diameter \>=17 mm, corresponding to an MIC \<2 μg/mL). We will include CRAB regardless of colistin, ampicillin-sulbactam, minocycline, tigecycline, trimethoprim/sulfamethoxazole and/or aminoglycoside susceptibility of the isolate. Attribution of the HAP/ VAP to CRAB will be allowed with isolation of CRAB from any respiratory sample within 7 days prior to the clinical diagnosis of pneumonia. Exclusion Criteria: * More than 72 hours of therapy with in-vitro coverage against the CRAB within 96 hours of enrolment * Polymicrobial carbapenem-susceptible infections: growth of other pathogens susceptible to carbapenems, or another beta-lactam, deemed clinically-significant by the treating physicians in blood or sputum (with HAP/ VAP). We will allow recruitment of patients with other carbapenem-resistant Gram-negative bacteria * CRAB susceptible any beta-lactam other than cefiderocol * Coronavirus 2019 (COVID-19) co-infection * Immediate-type hypersensitivity to penicillin * Pregnant women * Previous participation in the trial * Lack of informed consent, considering the procedures acceptable to ethics committees per locale, including deferred consent * Infection requiring treatment for over 14 days, at the discretion of the investigators * Life expectancy less than 24 hours or expected futility of antibiotic treatment
Where this trial is running
Haifa and 2 other locations
- Rambam Health Care Campus — Haifa, Israel (Recruiting)
- Sheba Tel HaShomer Medical Campus — Ramat Gan, Israel (Recruiting)
- Shamir Medical Center (Assaf Harofeh) — Tel Aviv, Israel (Recruiting)
Study contacts
- Principal investigator: Marco Falcone — Pisa University Hospital
- Study coordinator: Mical Paul
- Email: paulm@technion.ac.il
- Phone: 0502062140
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.